Role of Hydrogen Sulfide in Retinal Diseases

Abstract

As the third gasotransmitter, hydrogen sulfide (H₂S) plays a crucial role in the physiology and pathophysiology of many systems in the body, such as the nervous, cardiovascular, respiratory, and gastrointestinal systems. The mechanisms for its effects, including inhibiting ischemic injury, reducing oxidative stress damage, regulating apoptosis, and reducing the inflammation reaction in different systems, have not been fully understood. Recently, H₂S and its endogenous synthesis pathway were found in the mammalian retina. This review describes the production and the metabolism of H₂S and the evidence of a role of H₂S in the retina physiology and in the different retinal diseases, including retinal degenerative diseases and vascular diseases. In the retina, H₂S is generated in the presence of cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase from L-cysteine. The role of endogenous H₂S and its physiologic effect in the retina are still elusive. However, strong evidence shows that retina-derived H₂S might play protective or deleterious role in the pathogenesis of retinal diseases. For example, by regulating Ca²⁺ influx, H₂S can protect retinal neurons against light-induced degeneration. H₂S preconditioning can mediate the anti-apoptotic effect of retinal ganglion cells in retinal ischemia/reperfusion injury. Treatment with H₂S in rats relieves diabetic retinopathy by suppressing oxidative stress and reducing inflammation. Further studies would greatly improve our understanding of the pathophysiologic mechanisms responsible for retinal diseases and the potential for the H₂S-related therapy of the retinal diseases as well.

Keywords: H2S; neuromodulator; pathology; physiology; retinal degenerative diseases; retinal vascular diseases.

FIGURE 1

The role of endogenous H₂S in the physiologic and pathophysiologic regulation in the retina. 3MST, 3-mercaptopyruvate sulfurtransferase; BRB, blood–retina barrier; cAMP, cyclic adenosine monophosphate; CAT, cysteine aminotransferase; CBS, cystathionine-β-synthase; cGMP, cyclic guanosine monophosphate; CSE, cystathionine-γ-lyase; ERK, extracellular signal regulated kinase; GSH, glutathione; H₂S, hydrogen sulfide; I/R, ischemia/reperfusion; JNK, c-Jun N-terminal kinase; K_ATP, ATP-sensitive potassium channel; K_ir, inwardly rectifying potassium channel; K_v, voltage-dependent potassium channel; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor-κB; RGC, retinal ganglion cell; RPE, retinal pigment epithelial; VEGF, vascular endothelial growth factor.